Cutaneous manifestations of coronavirus disease 2019 patients in Japan.

Some patients with coronavirus disease 2019 (COVID-19) develop skin manifestations. There may be regional and racial differences in the frequency and type of COVID-19-associated skin manifestations. There are, however, few reports on skin manifestations in COVID-19 patients in Asia, including Japan. We retrospectively investigated the frequency, type, and clinical course of skin manifestations in Japanese patients with COVID-19. From 22 February 2020 to 16 August 2021, 738 Japanese patients (median age 59 years, 55% male) with laboratory-confirmed COVID-19 on polymerase chain reaction or antigen tests were admitted to our hospital. We mainly admitted patients with mild to moderate severity who had symptoms such as cough, fever, and oxygen demand but did not require mechanical ventilation. A total of 2.8% (21/738) of the COVID-19 patients treated at our hospital were diagnosed with viral eruptions caused by COVID-19. Of the 21 patients, 19 developed erythematous papules, and two developed urticaria. There were no cases of pernio-like lesions, known as COVID toes. The median duration from the onset of other COVID-19 symptoms to the development of skin manifestations was 9 days. This study revealed that approximately 2-3% of Japanese patients with COVID-19 developed COVID-19-associated viral eruptions, most of which were erythematous papules.

Three cases of COVID-19 patients presenting with erythema.

Individuals infected with the novel coronavirus (Severe Acute Respiratory Syndrome Coronavirus 2 [SARS-CoV-2]) who develop coronavirus disease 2019 (COVID-19) experience many symptoms; however, cutaneous manifestations are relatively rare. The authors encountered three patients with COVID-19 who presented with erythema and suspected viral rash. In all cases, erythema appeared after the onset of the initial symptoms of COVID-19. Erythema was considered to be caused by COVID-19 and not a drug-induced eruption because, in all cases, erythema was relieved merely by external medicine and oral antihistamines, without discontinuing the original medication. The authors' hospital accepted 69 COVID-19 patients between 22 February 2020 and 31 May 2020 and, of these, three (4.3%) exhibited eruptions, and all cases presented erythema. Except for seven patients who exhibited positive nasopharyngeal swab tests for SARS-CoV-2 RNA but no symptoms, three (4.8%) of the remaining 62 patients exhibited erythema. Although various types of eruptions have been reported in patients with COVID-19, erythema was the only type in our patients. Erythema in the three patients exhibited many similarities to that previously reported in COVID-19 patients, particularly in the manner it appeared and disappeared. For these reasons, these three cases were considered typical examples of erythema in patients with COVID-19. Considering previous studies and the three cases reported here, there is a high probability that SARS-CoV-2 can cause erythema.

Quality of life in Japanese couples during the transition to parenthood.

OBJECTIVE: This study aimed to examine the quality of life (QOL) in Japanese couples during the transition to parenthood with their first child. BACKGROUND: Relevant literature suggests that the health status of women drop during pregnancy and the postpartum period. However, less is known about their partner's well-being during the transition to parenthood and little research has addressed the relationship between couples' QOL across multiple domains. METHOD: Participants included 9216 married Japanese men and women, including 3729 couples, who were expecting or raising their first child under the age of three. They independently completed questionnaires on baseline demographics and on WHOQOL-BREF. RESULTS: Men showed higher scores for psychological QOL, while women had higher scores for social and environment QOL. A significant interaction between gender and stage of transition to parenthood was found. The moderating effect of age between the stage and QOL was found for men on the physical and psychological domains. Couples' QOL scores were weakly to moderately correlated. CONCLUSION: Findings suggest that both men and women had lower QOL, with the exception of women's physical QOL, after childbirth, but they showed different trends during the transition to parenthood across different domains of QOL.

Polyamine flux suppresses histone lysine demethylases and enhances ID1 expression in cancer stem cells.

Cancer stem cells (CSCs) exhibit tumorigenic potential and can generate resistance to chemotherapy and radiotherapy. A labeled ornithine decarboxylase (ODC, a rate-limiting enzyme involved in polyamine [PA] biosynthesis) degradation motif (degron) system allows visualization of a fraction of CSC-like cells in heterogeneous tumor populations. A labeled ODC degradation motif system allowed visualization of a fraction of CSC-like cells in heterogeneous tumor populations. Using this system, analysis of polyamine flux indicated that polyamine metabolism is active in CSCs. The results showed that intracellular polyamines inhibited the activity of histone lysine 4 demethylase enzymes, including lysine-specific demethylase-1 (LSD1). Chromatin immunoprecipitation with Pol II antibody followed by massively parallel DNA sequencing, revealed the global enrichment of Pol II in transcription start sites in CSCs. Increase of polyamines within cells resulted in an enhancement of ID1 gene expression. The results of this study reveal details of metabolic pathways that drive epigenetic control of cancer cell stemness and determine effective therapeutic targets in CSCs.

Identification of antifungal compounds in the spent mushroom substrate of Lentinula edodes.

In view of the possibility that spent mushroom substrates (SMSs) may be used as agricultural materials to prevent crop diseases, we examined the effect of treatment with a hot water extract from the SMS of Lentinula edodes on plant resistance to pathogenic infection. The extract of Le. edodes SMS was sprayed onto the leaves of rice plants, followed by inoculation of the leaves with the conidia of rice blast fungus. The development of lesions was suppressed by treatment with the SMS extract. The extract markedly inhibited the germination of Pyricularia oryzae conidia. We purified compounds 1, 2, and 3, which showed inhibitory effects on conidial germination, from the Le. edodes SMS extract of by successive solvent extraction, column chromatography, and preparative HPLC. Spectroscopic analyses revealed that 1, 2, and 3 were phenolic acids with two carboxyl groups in common.

4-(4-Hydroxyphenyl)-2-butanol (rhododendrol)-induced melanocyte cytotoxicity is enhanced by UVB exposure through generation of oxidative stress.

4-(4-Hydroxyphenyl)-2-butanol (rhododendrol, RD), a skin-whitening agent, was reported to cause skin depigmentation in some users, which is attributed to its cytotoxicity to melanocyte. It was reported that cytotoxicity to melanocyte is possibly mediated by oxidative stress in a tyrosinase activity-dependent manner. We examined the effect of UV radiation (UVR) on RD-induced melanocyte cytotoxicity as an additional aggravating factor. UVR enhanced RD-induced cytotoxicity in normal human epidermal melanocytes (NHEMs) via the induction of endoplasmic reticulum (ER) stress. Increased generation of intracellular reactive oxygen species (ROS) was detected. Pretreatment with N-acetyl cysteine (NAC), antioxidant and precursor of glutathione significantly attenuated ER stress-induced cytotoxicity in NHEMs treated with RD and UVR. Increase in cysteinyl-RD-catechol and RD-pheomelanin in NHEMs treated with RD and UVR suggested that, after UVR excitation, RD or RD metabolites are potent ROS-generating substances and that the tendency to produce RD-pheomelanin during melanogenesis amplifies ROS generation in melanocytes. Our results help to elucidate the development mechanisms of RD-induced leukoderma and provide information for innovation of safe skin-whitening compounds.

Characterization of human dental pulp cells grown in chemically defined serum-free medium.

Dental pulp cells (DPCs) are promising candidates for use as transplantable cells in regenerative medicine. However, ex vivo expansion of these cells typically requires culture media containing fetal bovine serum, which may cause infection and immunological reaction following transplantation. In addition, the proliferation and differentiation of DPCs markedly depend upon serum batches. Therefore, the present study examined whether DPCs could be expanded under serum-free conditions. DPCs obtained from four donors were identified to proliferate actively in the serum-free medium, STK2, when compared with those cells in control medium (Dulbecco's modified Eagle's medium containing 10% serum). The high proliferative potential with STK2 was maintained through multiple successive culture passages. DNA microarray analyses demonstrated that the gene expression profile of DPCs grown in STK2 was similar to that of cells grown in the control medium; however, a number of genes related to cell proliferation, including placental growth factor and inhibin-ßE, were upregulated in the STK2 cultures. Following induction of osteogenesis, DPCs grown in STK2 induced alkaline phosphatase activity and calcification at higher levels compared with the control medium cultures, indicating maintenance of differentiation potential in STK2. This serum-free culture system with DPCs may have applications in further experimental studies and as a clinical strategy in regenerative medicine.

Role of MSX1 in Osteogenic Differentiation of Human Dental Pulp Stem Cells.

Msh homeobox 1 (MSX1) encodes a transcription factor implicated in embryonic development of limbs and craniofacial tissues including bone and teeth. Although MSX1 regulates osteoblast differentiation in the cranial bone of young animal, little is known about the contribution of MSX1 to the osteogenic potential of human cells. In the present study, we investigate the role of MSX1 in osteogenic differentiation of human dental pulp stem cells isolated from deciduous teeth. When these cells were exposed to osteogenesis-induction medium, runt-related transcription factor-2 (RUNX2), bone morphogenetic protein-2 (BMP2), alkaline phosphatase (ALPL), and osteocalcin (OCN) mRNA levels, as well as alkaline phosphatase activity, increased on days 4-12, and thereafter the matrix was calcified on day 14. However, knockdown of MSX1 with small interfering RNA abolished the induction of the osteoblast-related gene expression, alkaline phosphatase activity, and calcification. Interestingly, DNA microarray and PCR analyses revealed that MSX1 knockdown induced the sterol regulatory element-binding protein 2 (SREBP2) transcriptional factor and its downstream target genes in the cholesterol synthesis pathway. Inhibition of cholesterol synthesis enhances osteoblast differentiation of various mesenchymal cells. Thus, MSX1 may downregulate the cholesterol synthesis-related genes to ensure osteoblast differentiation of human dental pulp stem cells.

DEC2 is a negative regulator for the proliferation and differentiation of chondrocyte lineage-committed mesenchymal stem cells.

Differentiated embryo chondrocyte 2 (DEC2) is a basic helix-loop-helix-Orange transcription factor that regulates cell differentiation in various mammalian tissues. DEC2 has been shown to suppress the differentiation of mesenchymal stem cells (MSCs) into myocytes and adipocytes. In the present study, we examined the role of DEC2 in the chondrogenic differentiation of human MSCs. The overexpression of DEC2 exerted minimal effects on the proliferation of MSCs in monolayer cultures with the growth medium under undifferentiating conditions, whereas it suppressed increases in DNA content, glycosaminoglycan content, and the expression of several chondrocyte-related genes, including aggrecan and type X collagen alpha 1, in MSC pellets in centrifuge tubes under chondrogenic conditions. In the pellets exposed to chondrogenesis induction medium, DEC2 overexpression downregulated the mRNA expression of fibroblast growth factor 18, which is involved in the proliferation and differentiation of chondrocytes, and upregulated the expression of p16INK4, which is a cell cycle inhibitor. These findings suggest that DEC2 is a negative regulator of the proliferation and differentiation of chondrocyte lineage-committed mesenchymal cells.

QOL and sociodemographic factors among first-time parents in Japan: a multilevel analysis.

PURPOSE: The present study aimed to examine the relationship between sociodemographic factors and domains of quality of life (QOL) among married adults in Japan who were either rearing or expecting their first child. Our research focus was on whether different sociodemographic variables interacted with each other in predicting the first-time parents' QOL. METHOD: In total, 4374 (mean age = 34.9 years, SD = 8.4, range 18-71) community-based married couples pooled from two surveys provided their sociodemographic information (i.e., age, years of education, and annual income) and responded to the brief version of the QOL instrument developed by the World Health Organization (WHOQOL-BREF in Psychological Medicine 28(3):551-555, 1998). RESULTS: Series of multilevel regression analyses revealed that household annual income and education were associated with all domains of QOL, and other sociodemographic variables worked in a domain-specific manner. In addition, the effect of educational attainment on psychological domain was significant for mothers only, whereas the effects of household income on psychological and environmental domains were stronger for the younger (below age 26) than the older (over 43) couples. CONCLUSION: The effects of sociodemographic factors at couple as well as individual levels on the first-time parents' QOL were examined for the first time in Japan using couple data. In addition to corroborating previous findings on the main effects concerning these variables, the present study demonstrated the complex patterns of interaction across different levels. These findings provide evidence for the need for financial and health measures targeted at specific parent populations.

Detection of UV-induced cyclobutane pyrimidine dimers by near-infrared spectroscopy and aquaphotomics.

Ultraviolet (UV) radiation causes cellular DNA damage, among which cyclobutane pyrimidine dimers (CPDs) are responsible for a variety of genetic mutations. Although several approaches have been developed for detection of CPDs, conventional methods require time-consuming steps. Aquaphotomics, a new approach based on near-infrared spectroscopy (NIRS) and multivariate analysis that determines interactions between water and other components of the solution, has become an effective method for qualitative and quantitative parameters measurement in the solutions. NIR spectral patterns of UVC-irradiated and nonirradiated DNA solutions were evaluated using aquaphotomics for detection of UV-induced CPDs. Groups of UV-irradiated and nonirradiated DNA samples were classified (87.5% accuracy) by soft independent modeling of class analogy (SIMCA). A precise regression model calculated from NIR water spectral patterns based on UVC doses (r Val = 0.9457) and the concentration of cis-syn cyclobutane thymine dimers (cis-syn T<>Ts; r Val = 0.9993) was developed using partial least squares regression (PLSR), while taking advantage of water spectral patterns, particularly around 1400-1500 nm. Our results suggested that, in contrast to DNA, the formation of cis-syn T<>Ts increased the strongly hydrogen bonded water. Additionally, NIRS could qualitatively and quantitatively detect cis-syn T<>Ts in isolated DNA aqueous solutions upon UVC exposure.

Characteristic expression of MSX1, MSX2, TBX2 and ENTPD1 in dental pulp cells.

Dental pulp cells (DPCs) are a promising source of transplantable cells in regenerative medicine. However, DPCs have not been fully characterized at the molecular level. The aim of the present study was to distinguish DPCs from various source-derived mesenchymal stem cells (MSCs), fibroblasts (FBs) and other cells by the expression of several DPC-characteristic genes. DPCs were isolated from human pulp tissues by the explant method or the enzyme digestion method, and maintained with media containing 10% serum or 7.5% platelet-rich plasma. RNA was isolated from the cells and from dental pulp tissue specimens. The mRNA levels were determined by DNA microarray and quantitative polymerase chain reaction analyses. The msh homeobox 1, msh homeobox 2, T-box 2 and ectonucleoside triphosphate diphosphohydrolase 1 mRNA levels in DPCs were higher than that of the levels identified in the following cell types: MSCs derived from bone marrow, synovium and adipose tissue; and in cells such as FBs, osteoblasts, adipocytes and chondrocytes. The enhanced expression in DPCs was consistently observed irrespective of donor age, tooth type and culture medium. In addition, these genes were expressed at high levels in dental pulp tissue in vivo. In conclusion, this gene set may be useful in the identification and characterization of DPCs in basic studies and pulp cell-based regeneration therapy.

The psychometric properties of the WHOQOL-BREF in Japanese couples.

This study investigated the psychometric properties of the Japanese version of the WHOQOL-BREF among 10,693 community-based married Japanese men and women (4376 couples) who were either expecting or raising a child. Analyses of item-response distributions, internal consistency, criterion validity, and discriminant validity indicated that the scale had acceptable reliability and performed well in preliminary tests of validity. Furthermore, dyadic confirmatory factor analysis revealed that the theoretical factor structure was valid and similar across partners, suggesting that men and women define and value quality of life in a similar way.

The ordered acquisition of Class II and Class I mutations directs formation of human t(8;21) acute myelogenous leukemia stem cell.

The cellular properties of leukemia stem cells (LSCs) are achieved at least through Class I and Class II mutations that generate signals for enhanced proliferation and impaired differentiation, respectively. Here we show that in t(8;21) acute myelogenous leukemia (AML), hematopoietic stem cells (HSCs) transform into LSCs via definitively-ordered acquisition of Class II (AML1/ETO) and then Class I (c-KIT mutant) abnormalities. Six t(8;21) AML patients with c-KIT mutants maintaining > 3 years of complete remission were analyzed. At diagnosis, all single LSCs had both AML1/ETO and c-KIT mutations. However, in remission, 16 out of 1,728 CD34(+)CD38(-) HSCs and 89 out of 7,187 single HSC-derived myeloerythroid colonies from these patients had AML1/ETO, whose breakpoints were identical to those found in LSCs. These cells had wild-type c-KIT, which expressed AML1/ETO at a low level, and could differentiate into mature blood cells, suggesting that they may be the persistent preleukemic stem cells. Microarray analysis suggested that mutated c-KIT signaling provides LSCs with enhanced survival and proliferation. Thus, in t(8;21) AML, the acquisition of AML1/ETO is not sufficient, and the subsequent upregulation of AML1/ETO and the additional c-KIT mutant signaling are critical steps for transformation into LSCs.

Successful treatment of Rosai-Dorfman disease with low-dose oral corticosteroid.

We present herein a Japanese case of Rosai-Dorfman disease (RDD) in which cutaneous manifestations completely remitted after treatment with low-dose oral corticosteroid. A 69-year-old Japanese man presented with a 1-year history of enlarged submandibular lymph nodes and subsequent nasal and pharyngeal bleeding. RDD was diagnosed based on biopsy results from a lymph node in the left parotid region. The patient had also noted several skin eruptions that repeatedly appeared and disappeared on the face and arms. Biopsies were taken from skin eruptions on the face and cuboidal fossa. Both biopsy specimens showed dense, well-demarcated infiltration of histiocytes, lymphocytes and multinucleated giant cells from just under the epidermis to the subcutaneous tissue. These histiocytes were positive for CD68 and S-100, but negative for CD1a, and some displayed emperipolesis. Given the histopathological findings and the fact that the patient was suffering from RDD, skin lesions were diagnosed as cutaneous manifestations of RDD. Cutaneous lesions gradually began to persist concomitant with enlargement of extranodal lymphadenopathy in the nasopharyngeal area. Increasing respiratory obstruction prompted a trial with oral prednisolone commencing at 0.4 mg/kg per day. Both the lymphadenopathy and skin lesions responded quickly. Within 3 months, all his skin lesions disappeared completely with almost complete resolution of lymphadenopathy. Twelve months after the beginning of oral prednisolone therapy, slight recurrence of mucosal and cutaneous lesions appeared, but disappeared quickly with an increase in prednisolone to 0.3 mg/kg per day. Low-dose prednisolone appeared very effective in the case of RDD.

Magnetic resonance findings of primary uterine malignant lymphoma.

To clarify the magnetic resonance (MR) characteristics of primary uterine malignant lymphoma, we identified 4 patients with primary uterine lymphoma in the MR database of our institute from 1994 to 2005 and evaluated their clinical and MR findings for tumor extension, size, shape, and signal intensity, multinodular growth pattern, preservation of normal endometrium, and lymphadenopathy. In all 4 patients, tumors extended to the uterus and vagina or parametrium, and uterine tumors showed relatively homogeneous intensity on both T(1)- and T(2)-weighted MR imaging. Two patients showed multinodular tumor growth; three revealed pelvic lymphadenopathy; and none had intact endometrium or normal uterine zonal structure. Thus, large tumors with relatively homogeneous signal intensity seemed to be a specific MR finding of uterine lymphoma, and findings of multinodular growth were considered a possible characteristic suggesting the uterine involvement of malignant lymphoma.

[The laboratory diagnosis of influenza viruses].

The methods of the pathogen diagnosis for confirm the infection of the influenza virus, there are the viral isolation and the method of detected the viral antigen. In the each method of inspection, the time of sample extraction, the method of extraction and preservation must be suited to fully improve the sensitivity and specificity. The viral isolation is necessary and indispensable to analyze the antigen of the epidemic viruses and it is the high level of sensitivity. The several methods of detecting the antigen of the gene amplification include the reverse transcription polymerase chain reaction (RT-PCR) method, the loop-mediated isothermal amplification (LAMP) method, the real-time PCR method, and the nucleic acid sequence-based amplification (NASBA) method, and these methods are excellent promptly. As for these detection methods, being chosen according to the purpose is desirable.